PMID- 10657992
OWN - NLM
STAT- MEDLINE
DCOM- 20000303
LR  - 20190516
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 14
IP  - 2
DP  - 2000 Feb
TI  - Enzyme replacement therapy in a mouse model of aspartylglycosaminuria.
PG  - 361-7
AB  - Aspartylglycosaminuria (AGU), the most common lysosomal disorder of glycoprotein 
      degradation, is caused by deficient activity of glycosylasparaginase (AGA).
      AGA-deficient mice share most of the clinical, biochemical and histopathologic
      characteristics of human AGU disease. In the current study, recombinant human AGA
      administered i.v. to adult AGU mice disappeared from the systemic circulation of 
      the animals in two phases predominantly into non-neuronal tissues, which were
      rapidly cleared from storage compound aspartylglucosamine. Even a single AGA
      injection reduced the amount of aspartylglucosamine in the liver and spleen of
      AGU mice by 90% and 80%, respectively. Quantitative biochemical analyses along
      with histological and immunohistochemical studies demonstrated that the
      pathophysiologic characteristics of AGU were effectively corrected in
      non-neuronal tissues of AGU mice during 2 wk of AGA therapy. At the same time,
      AGA activity increased to 10% of that in normal brain tissue and the accumulation
      of aspartylglucosamine was reduced by 20% in total brain of the treated animals. 
      Immunohistochemical studies suggested that the corrective enzyme was widely
      distributed within the brain tissue. These findings suggest that AGU may be
      correctable by enzyme therapy.-Dunder, U., Kaartinen, V., Valtonen, P., Vaananen,
      E., Kosma, V.-M., Heisterkamp, N., Groffen, J., Mononen, I. Enzyme replacement
      therapy in a mouse model of aspartylglycosaminuria.
FAU - Dunder, U
AU  - Dunder U
AD  - Department of Clinical Chemistry, Kuopio University Hospital, FIN-70211 Kuopio,
      Finland.
FAU - Kaartinen, V
AU  - Kaartinen V
FAU - Valtonen, P
AU  - Valtonen P
FAU - Vaananen, E
AU  - Vaananen E
FAU - Kosma, V M
AU  - Kosma VM
FAU - Heisterkamp, N
AU  - Heisterkamp N
FAU - Groffen, J
AU  - Groffen J
FAU - Mononen, I
AU  - Mononen I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 2776-93-4 (N-acetylglucosaminylasparagine)
RN  - EC 3.5.1.26 (Aspartylglucosylaminase)
RN  - V956696549 (Acetylglucosamine)
SB  - IM
MH  - Acetylglucosamine/*analogs & derivatives/urine
MH  - Animals
MH  - Aspartylglucosylaminase/pharmacokinetics/*therapeutic use
MH  - Half-Life
MH  - Kidney/pathology
MH  - Liver/pathology
MH  - Lysosomal Storage Diseases/*drug therapy
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Spleen/pathology
MH  - Tissue Distribution
EDAT- 2000/02/05 09:00
MHDA- 2000/03/11 09:00
CRDT- 2000/02/05 09:00
PHST- 2000/02/05 09:00 [pubmed]
PHST- 2000/03/11 09:00 [medline]
PHST- 2000/02/05 09:00 [entrez]
AID - 10.1096/fasebj.14.2.361 [doi]
PST - ppublish
SO  - FASEB J. 2000 Feb;14(2):361-7. doi: 10.1096/fasebj.14.2.361.